Primary prevention of asthma
FACTORS ASSOCIATED WITH INCREASED OR DECREASED RISK OF ASTHMA IN CHILDREN
Nutrition of mother and baby Maternal diet
For some time, the mother’s diet during pregnancy has been a focus of concern relating to the development of allergy and asthma in the child. There is no firm evidence that ingestion of any specific foods during pregnancy increases the risk for asthma. However, a recent study of a pre-birth cohort observed that maternal intake of foods commonly
considered allergenic (peanut and milk) was associated with a decrease in allergy and asthma in the offspring.671 Similar data have been shown in a very large Danish National birth cohort, with an association between ingestion of peanuts, tree nuts and/or fish during pregnancy and a decreased risk of asthma in the offspring.672,673 Epidemiological studies and randomized controlled trials on maternal dietary intake of fish or long-chain polyunsaturated fatty acids during pregnancy showed no consistent effects on the risk of wheeze, asthma or atopy in the child.674-677 Dietary changes during
pregnancy are therefore not recommended for prevention of allergies or asthma.
Maternal obesity and weight gain during pregnancy
Data suggest that maternal obesity and weight gain during pregnancy pose an increased risk for asthma in children. A recent meta-analysis678 showed that maternal obesity in pregnancy was associated with higher odds of ever asthma or wheeze or current asthma or wheeze; each 1 kg/m2 increase in maternal BMI was associated with a 2% to 3% increase in the odd of childhood asthma. High gestational weight gain was associated with higher odds of ever asthma or
wheeze. However, no recommendations can be made at present, as unguided weight loss in pregnancy should not be encouraged.
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Breast-feeding
Despite the existence of many studies reporting a beneficial effect of breast-feeding on asthma prevention, results are conflicting,403 and caution should be taken in advising families that breast-feeding will prevent asthma.679 Breast-feeding decreases wheezing episodes in early life; however, it may not prevent development of persistent asthma (Evidence D).
Regardless of its effect on development of asthma, breast-feeding should be encouraged for all of its other positive benefits (Evidence A).
Delayed introduction of solids
Beginning in the 1990s, many national pediatric agencies and societies recommended delay of introduction of solid food, especially for children at a high risk for developing allergy. Current guidelines do not recommend strict avoidance of high-risk foods,403 but carefully controlled, prospective studies are needed to conclusively resolve this controversy.
Dietary supplements for mothers and/or babies Vitamin D
Intake of vitamin D may be through diet, dietary supplementation or sunlight. A systematic review of cohort, case control and cross-sectional studies concluded that maternal dietary intake of vitamin D, and of vitamin E, was associated with lower risk of wheezing illnesses in children.680 This was not confirmed in two randomized controlled trials of vitamin D supplementation in pregnancy, although a significant effect was not ruled out.681,682 When the results from these two trials were combined, there was a 25% reduction of risk of asthma/recurrent wheeze at ages 0-3 years.683 The effect was greatest among women who maintained 25(OH)vitamin D levels of at least 30ng/ml from the time of study entry through delivery, suggesting that sufficient levels of Vitamin D during early pregnancy may be important in decreasing risk for early life wheezing episodes.683
Fish oil and long-chain polyunsaturated fatty acids
Systematic reviews of cohort studies about maternal dietary intake of fish or seafood during pregnancy674,684 and of randomized controlled trials on maternal dietary intake of fish or long-chained polyunsaturated fatty acids during pregnancy674 showed no consistent effects on the risk of wheeze, asthma or atopy in the child. One recent study
demonstrated decreased wheeze/asthma in pre-school children at high risk for asthma when mothers were given a high dose fish oil supplement in the third trimester;685 however ‘fish oil’ is not well defined, and the optimal dosing regimen has not been established.
Probiotics
A meta-analysis provided insufficient evidence to recommend probiotics for the prevention of allergic disease (asthma, rhinitis, eczema or food allergy).686
Inhalant allergens
Sensitization to indoor, inhaled aero-allergens is generally more important than sensitization to outdoor allergens for the presence of, and/or development of, asthma. While there appears to be a linear relationship between exposure and sensitization to house dust mite,687,688 the relationship for animal allergen appears to be more complex.403 Some studies have found that exposure to pet allergens is associated with increased risk of sensitization to these allergens,689,690 and of asthma and wheezing.691,692 By contrast, other studies have demonstrated a decreased risk of developing allergy with exposure to pets.693,694 A review of over 22,000 school-age children from 11 birth cohorts in Europe found no correlation between pets in the homes early in life and higher or lower prevalence of asthma in children.695 For children at risk of asthma, dampness, visible mold and mold odor in the home environment are associated with increased risk of
developing asthma.696 Overall, there are insufficient data to recommend efforts to either reduce or increase pre-natal or early-life exposure to common sensitizing allergens, including pets, for the prevention of allergies and asthma.
Birth cohort studies provide some evidence for consideration. A meta-analysis found that studies of interventions focused on reducing exposure to a single allergen did not significantly affect asthma development, but that multifaceted
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interventions such as in the Isle of Wight study,697 the Canadian Asthma Primary Prevention Study,698 and the
Prevention of Asthma in Children study699 were associated with lower risk of asthma diagnosis in children younger than 5 years.700 Two multifaceted studies that followed children beyond 5 years of age demonstrated a significant protective effect both before and after the age of 5 years.697,701 The Isle of Wight study has shown a continuing positive benefit for early-life intervention through to 18 years of age;702 however, exactly which components of the intervention were important and which specific mechanistic changes were induced remain elusive.
Treatment with grass SLIT for 3 years did not reduce the incidence of asthma diagnosis (primary outcome) in a large randomized double-blind placebo-controlled trial in children 5-12 years with grass-allergic rhinoconjunctivitis, but asthma symptoms and asthma medication use were reduced. At present, SLIT for children with grass allergic rhinoconjunctivitis is not recommended for asthma prevention.703 Additional studies are needed.
Pollutants
Maternal smoking during pregnancy is the most direct route of pre-natal environmental tobacco smoke exposure.704 A meta-analysis concluded that pre-natal smoking had its strongest effect on young children, whereas post-natal maternal smoking seemed relevant only to asthma development in older children.705 Exposure to outdoor pollutants, such as living near a main road, is associated with increased risk of asthma.706,707 Prenatal NO2, SO2, and PM10 exposures are associated with an increased risk of asthma in childhood,708 but it is difficult to separate pre- and post-natal exposure.
Microbial effects
The ‘hygiene hypothesis’, and the more recently coined ‘microflora hypothesis’ and ‘biodiversity hypothesis’,709 suggest that human interaction with microbiota may be beneficial in preventing asthma. For example, there is a lower risk of asthma among children raised on farms with exposure to stables and consumption of raw farm milk than among children of non-farmers.710 The risk of asthma is also reduced in children whose bedrooms have high levels of bacterial-derived lipopolysaccharide endotoxin.711,712Similarly, children in homes with ≥2 dogs or cats are less likely to be allergic than those in homes without dogs or cats.694 Exposure of an infant to the mother’s vaginal microflora through vaginal delivery may also be beneficial; the prevalence of asthma is higher in children born by cesarean section than those born
vaginally.713,714 This may relate to differences in the infant gut microbiota according to their mode of delivery.715 Respiratory syncytial virus infection is associated with subsequent recurrent wheeze, and preventative treatment of premature infants with monthly injections of the monoclonal antibody, palivizumab, (prescribed for prophylaxis of respiratory syncytial virus) is associated with a reduction in recurrent wheezing in the first year of life.716 However, there is little evidence to suggest that this effect is sustained. Although the risk of parent-reported asthma with infrequent wheeze was reduced at 6 years, there was no impact on doctor-diagnosed asthma or lung function.717 Thus, the long-term effect of palivizumab in the prevention of asthma remains uncertain.
Medications and other factors
Antibiotic use during pregnancy and in infants and toddlers has been associated with the development of asthma later in life,718-720 although not all studies have shown this association.721 Intake of the analgesic, paracetamol (acetaminophen), may be associated with asthma in both children and adults,722 although exposure during infancy may be confounded by use of paracetamol for respiratory tract infections.722 Frequent use of paracetamol by pregnant women has been
associated with asthma in their children.723 There is no evidence that vaccinations increase the risk of a child developing asthma.
Psychosocial factors
The social environment to which children are exposed may also contribute to the development and severity of asthma.
Maternal distress during pregnancy724 or during the child’s early years718 has been associated with an increased risk of the child developing asthma.